ArticleJournal of cancer research and clinical oncology2020
Senescent hepatic stellate cells caused by deoxycholic acid modulates malignant behavior of hepatocellular carcinoma.
Article in Journal of cancer research and clinical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Dysregulation of serum bile acids in liver cancer: a systematic review and meta-analysis.Metabolomics : Official journal of the Metabolomic Society · 2025Pooled it
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- Senescent cells in systemic aging: SASP heterogeneity, immune escape, and endocrine modulation.Biogerontology · 2026Review
- Altered Bile Acid Transport in Liver Disease.Biomedicines · 2026Review
- Effects of Ritonavir, Lopinavir, and Alcohol on ABC Transporters and Secretion of Bile Acid and Bilirubin in Senescent Hepatocytes.International journal of molecular sciences · 2026Article
- The landscape of gut microbiota in hepatocarcinogenesis: a comprehensive review of pathogenesis and therapeutic interventions.International journal of surgery (London, England) · 2026Review
- Cellular senescence in liver diseases: From molecular drivers to therapeutic targeting.Journal of hepatology · 2026Review
- Clinical and biological significance of the relationship between gut microbiota and liver disease.World journal of hepatology · 2025Review
- Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.Current oncology (Toronto, Ont.) · 2025Review
- Multifaceted roles of microbiota-derived deoxycholic acid in gastrointestinal cancers: from barrier disruption to therapeutic implications.Human cell · 2025Review
- The Roles and Clinical Significance of Major Hepatic-Derived Metabolites in Hepatocellular Carcinoma.Journal of gastroenterology and hepatology · 2025Review
- Fibroblast growth factor 19-fibroblast growth factor receptor 4 axis: From oncogenesis to targeted-immunotherapy in advanced hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Review
- Type 2 Diabetes and the Multifaceted Gut-X Axes.Nutrients · 2025Review
- Preoperative total bile acid can be used as a prognostic biomarker in patients with operable biliary tract cancers.Discover oncology · 2025Article
- Circulating bile acid profiles characteristics and the potential predictive role in clear cell renal cell carcinoma progression.BMC nephrology · 2025Article
- Emerging role of bile acids in colorectal liver metastasis: From molecular mechanism to clinical significance (Review).International journal of oncology · 2025Review
- Gut microbiome and liver diseases.Fundamental research · 2025Review
- Gut‑liver axis in liver disease: From basic science to clinical treatment (Review).Molecular medicine reports · 2025Review
- Multi-Omics Analysis and Validation of Cell Senescence-Related Genes Associated with Non-Alcoholic Fatty Liver Disease.Journal of inflammation research · 2025Article
- Iron chelation as a new therapeutic approach to prevent senescence and liver fibrosis progression.Cell death & disease · 2024Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeDeoxycholic acid (DCA), a secondary bile acid, is reportedly increased in the serum of patients with nonalcoholic steatohepatitis and animals with experimentally induced hepatocellular carcinoma (HCC), but its contribution to malignant behaviors of HCC has not been precisely clarified. This study aimed to examine the effect of DCA on hepatic stellate cells (HSCs), a major component of nonparenchymal cells in the liver, and its subsequent indirect effect on HCC cells.
methodsLX2 cells, a human HSC line, were treated with DCA in vitro. Then, HuH7 cells, a human hepatoma cell line, were incubated in conditioned media of DCA-treated LX2 to investigate the subsequent effect focusing on malignant behaviors.
resultsDCA resulted in cellular senescence in LX2 with the decreased cell proliferation via cell cycle arrest at G0/1 phase, together with the induction of senescence-associated secretory phenotype (SASP) factors. To investigate the influence of SASP factors secreted by HSCs in response to DCA, HCC cells were treated with conditioned media that promoted cell migration and invasion via induction of epithelial mesenchymal transition. These changes were attenuated in the presence of neutralizing antibody against IL8 or TGFβ. Pathological analysis of surgical specimens from HCC patients revealed that senescent HSCs were detected in the stroma surrounding HCC.
conclusionOur data suggest an important role of HSC senescence caused by DCA for the malignant biological behaviors of HCC via induction of SASP factors, particularly IL8 and TGFβ.
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